Decreasing ambient oxygen tension increases the rates of cell division of cardiac and other cell types in tissue culture and in neonatal rat. Increasing ambient oxygen retards such growth. In such oxygen mediated regulation of cell division we shall explore the role of poly (ADP-ribose) polymerase, an enzyme that splits off nicotinamide from NAD ion and polymerizes its ADP-ribose moiety to form the polynucleotide poly (ADP-ribose). Located in the nucleus, poly (ADP-ribose) inhibits DNA synthesis in normal cells. We believe that oxygen, by controlling the ratio of NAD ion/NADH will regulate the concentration of the inhibitor, poly ADP-ribose. Thus low oxygen, known to augment the rate of cell division, would shift NAD ion to NADH and thereby remove precursor for poly (ADP-ribose). As a result DNA synthesis would be less supressed and the rate of cell division would increase. Activity of both poly (ADP-ribose) polymerase and glycohydrolase (which degrades poly ADP-ribose) will be measured in chick heart cells grown in 5% and 20% oxygen in tissue culture. Activity of both enzymes will also be measured in fetal and adult tissue to assess their role in normal development. Enzyme activity will be measured first in whole cell homogenates while techniques for isolation of nuclei from cardiac muscle are perfected. Then activity of nuclei as well as quantity of purified enzyme will be measured. Preliminary experiments suggest that the poly (ADP-ribose) polymerase system may well be an important molecular site of action by which oxygen regulated rates of cell division.